What can the 49ers defense accomplish with Patrick Willis on the field?

For the first time in three weeks, they will find out today as the All-Pro inside linebacker is active for their meeting against the visiting Cardinals after being sidelined with a groin injury.

Without Willis, the 49ers have allowed 250.5 yards a game, one touchdown and 14 points in blowout wins over the Rams (35-11) and Texans (34-3).

The 49ers, of course, have also played the past two weeks with All-Pro outside linebacker Aldon Smith, who is in a treatment facility for a reported substance-abuse problem.

According to an ESPN report today, the 49ers are “not counting on” Smith to return to the team this season, believing his off-the-field issues are so severe they could delay his return until 2014. Smith has been charged with DUI twice since January of 2012 and is also facing three felony counts of illegal possession of an assault weapon. Smith will face a suspension from the NFL, which could be served next season once the legal process has played out.

In Smith’s absence, his spot has been manned by five-year veteran Dan Skuta and rookie Corey Lemonier, who was the subject of this feature story in today’s Chronicle. Lemonier has played 78 snaps in the past two games, while Skuta has played 74.

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Running back LaMichael James and cornerback Nnamdi Asomugha are healthy scratches for the 49ers.

Since returning from a knee injury sustained in the preseason finale, James has 31 yards on 7 carries in two games. Without James, Frank Gore, Kendall Hunter and Anthony Dixon will be the 49ers running backs.

Fangio said this week that Asomugha could be inactive on game days as long as Tramaine Brock remained the No. 3 cornerback.